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Mechanism Of Action

Pompe disease (acid maltase deficiency, glycogen storage disease type II, GSD II, glycogenosis type II) is an inherited disorder of glycogen metabolism caused by the absence or marked deficiency of the lysosomal enzyme GAA.

LUMIZYME provides an exogenous source of GAA. Binding to mannose-6-phosphate receptors on the cell surface has been shown to occur via carbohydrate groups on the GAA molecule, after which it is internalized and transported into lysosomes, where it undergoes proteolytic cleavage that results in increased enzymatic activity. It then exerts enzymatic activity in cleaving glycogen.


Clinical pharmacodynamic studies have not been conducted for LUMIZYME.


The pharmacokinetics of alglucosidase alfa were studied in 32 late-onset Pompe disease patients from the randomized, doubleblind, placebo-controlled study ranging in age from 21 to 70 years old who received LUMIZYME 20 mg/kg every other week. The pharmacokinetics were not time-dependent for patients who did not develop high antibody titer/inhibitory antibody. Parameter values did not change across visits at Weeks 0, 12, and 52. At Week 52 of bi-weekly administration the estimates of AUC (2700 mcg•h/mL with 30.4% coefficient of variation [CV],n=29), Cmax (372 mcg /mL with 22.7% CV,n=29) and clearance (601 mL/h with 28.2% CV,n=29) were determined at steady-state. The declining portion of the concentration-time profile of alglucosidase alfa appears biphasic within the observed sampling time. The half-life for the first phase is 2.4 hours with a between subject variation of 10%. Concentrations of alglucosidase alfa were not sampled long enough to adequately determine the half-life for the second phase.

Higher mean clearance (42%) was observed at Week 52 in 4 of 5 patients that tested positive for antibodies that inhibit the cellular uptake of enzyme. Pharmacokinetics in 4 of these 5 individuals over time indicated an increase in clearance with increase in IgG titer. Positive inhibitory antibody status correlated with higher IgG titers in patients who received LUMIZYME. The relationship between exposure and efficacy has not been defined.

Clinical Studies

Controlled Clinical Trials

The safety and efficacy of LUMIZYME was assessed in 90 patients with late-onset Pompe disease, ages 10 to 70 years, in a randomized double-blind, placebo-controlled study designed to enroll patients age 8-70 years. The youngest LUMIZYMEtreated patient was 16 years of age, and the youngest placebotreated patient was 10 years of age. All patients were naive to enzyme replacement therapy. Patients were allocated in a 2:1 ratio and received 20 mg/kg LUMIZYME (n=60) or placebo (n=30) every other week for 78 weeks (18 months). The study population included 34 males and 26 females (N=60) in the LUMIZYME group and 11 males and 19 females (N=30) in the placebo group. At baseline, all patients were ambulatory (some required assistive walking devices), did not require invasive ventilator support or non-invasive ventilation while awake and sitting upright and had a forced vital capacity (FVC) between 30 and 79% of predicted in the sitting position. Patients who could not walk 40 meters in 6 minutes or were unable to perform appropriate pulmonary and muscle function testing were excluded from the study.

A total of 81 of 90 patients completed the study. Of the 9 patients who discontinued, 5 were in the LUMIZYME group and 4 were in the placebo group. Three patients discontinued the study due to an adverse event; two patients were in the LUMIZYME treatment group and one patient was in placebo group. One patient in the LUMIZYME group died [see ADVERSE REACTIONS]. Four patients discontinued study participation to pursue treatment with commercial therapy, and one patient discontinued the study for personal reasons. At study entry, the mean % predicted FVC in the sitting position among all patients was about 55%. After 78 weeks, the mean % predicted FVC increased to 56.2% for LUMIZYME-treated patients and decreased to 52.8% for placebo-treated patients indicating a LUMIZYME treatment effect of 3.4% (95% confidence interval: [1.3% to 5.5%]; p=0.004). Stabilization of % predicted FVC in the LUMIZYME-treated patients was observed (see Figure 1).

Figure 1: Mean FVC Upright (% Predicted) Over Time

Mean FVC Upright (% Predicted) Over Time - Illustration

At study entry, the mean 6 minute walk test (6MWT) among all patients was about 330 meters. After 78 weeks, the mean 6MWT increased by 25 meters for LUMIZYME-treated patients and decreased by 3 meters for placebo-treated patients indicating a LUMIZYME treatment effect of 28 meters (95% confidence interval: [-1 to 52 meters]; p=0.06) (see Figure 2).

Figure 2: Mean Six Minute Walk Test Total Distance Walked Over Time

Mean Six Minute Walk Test Total Distance Walked Over Time - Illustration

Uncontrolled Studies

The effectiveness of LUMIZYME has not been established in infantile-onset patients. Descriptive data from infantile-onset patients who have received LUMIZYME commercially outside the U.S. have been collected in the Pompe Registry. The Pompe Registry is a multi-center, multi-national, voluntary, observational disease registry. Fifteen infantile-onset patients enrolled in the registry were matched to the baseline characteristics of an untreated historical control cohort. These patients were diagnosed with Pompe disease and received treatment with LUMIZYME prior to 6 months of age (range 0.6 to 6 months). The median duration of treatment was 15 months (range 3 to 48 months). Estimated survival in LUMIZYMEtreated patients was 57% at 18 months and 37% at 36 months, compared to the 2% survival in the historical control group at both time points. The median age of death or last follow-up was 19 months (range 5 to 51 months).

Descriptive clinical data from patients with infantile-onset Pompe disease in the Pompe Registry were used to verify the overall effectiveness of LUMIZYME for patients 8 years and older with late-onset Pompe disease.

Last reviewed on RxList: 7/14/2014
This monograph has been modified to include the generic and brand name in many instances.


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